1. Field of the Invention
The present invention relates to a non-invasive apparatus for detecting and identifying microorganisms in a specimen such as blood, where the specimen and a culture medium are introduced into a large number of sealable blood culture vials and are exposed to conditions enabling a variety of metabolic, physical, and chemical changes to take place in the presence of microorganisms in the sample. These changes are monitored using colorimetric or fluorescent chemical sensors that are disposed on the inner bottom surface of each blood culture bottle.
2. Background Description
The presence of biologically active agents such as bacteria in a patient's body fluid, especially blood, is generally determined using blood culture containers. A small quantity of blood is injected through an enclosing rubber septum into a sterile container containing a culture medium, and the container is then incubated at 37.degree. C. and monitored for microorganism growth.
One of the techniques used to detect the presence of microorganisms includes visual inspection. Generally, visual inspection involves monitoring the turbidity or eventual color changes of the liquid suspension of blood and culture medium. Known instrumental methods detect changes in the carbon dioxide content of the culture bottles, which is a metabolic by-product of the bacterial growth. Monitoring the carbon dioxide content can be accomplished by methods well established in the art, such as radiochemical or infrared absorption at a carbon dioxide spectral line. Until now, these methods have required invasive procedures which result in the well-known problem of cross-contamination between different containers. It has also been proposed to detect microorganism growth in sealable containers by monitoring positive and/or negative pressure changes.
Recently, non-invasive methods have been developed involving chemical sensors disposed inside the container. These sensors respond to changes in the carbon dioxide concentration by changing their color or by changing their fluorescence intensity. In known automated non-invasive blood culture systems, individual light sources, spectral excitation/emission filters, and photodetectors are arranged adjacent to each container. This results in station sensitivity variations from one container to the next. Therefore, extensive and time-consuming calibration procedures are required to operate such systems. In addition, flexible electrical cables are required to connect the individual sources and detectors with the rest of the instrument. With the large number of light sources, typically 240 or more per instrument, maintenance can become very cumbersome and expensive when individual sources start to fail.
In known colorimetric or fluorometric instruments, light emitting diodes ("LEDs") are used as the individual light sources. These sources have only a relatively low optical output power. Therefore, high photometric detection sensitivity is required to monitor the container sensor emissions. This results in additional and more complicated front-end electronics for each photodetector, increasing production cost. To reduce equipment cost and complexity, it has been proposed to use optical fibers at each container to feed the output light of an instrument's sensors to a central photodetector. A disadvantage to this approach is the need for arranging a large number of relatively long fibers of different length within the instrument.
In U.S. Pat. No. 5,518,923 it has been proposed to arrange a multitude of blood culture bottles on a rotating turntable with sensor stations mounted behind the turntable such that the sensor stations can monitor the bottles. In particular, as the turntable rotates, each bottle pass a sensor station and is interrogated for microorganism growth. It has also been proposed to perform a presumptive microorganism identification by monitoring more than one analyte per vial and analyzing the time behavior of the corresponding growth curves. (See U.S. Pat. No. 5,217,875.) However, in practice it has been found that with vials placed on a rotating turntable, the agitation of the liquid is insufficient and results in diffusion-limited growth curves. In other words, the time behavior of the growth curves is dominated by the size of the gas-liquid interface and the sensor response time, and only to a lesser degree by the metabolic characteristics of the microorganism population which can be a problem if organism identification is being attempted via growth curve analysis.